The U.S. trial enrolled patients aged 40 and older with knee pain due to osteoarthritis.
They were randomly assigned to one of five treatments:

Inactive
placebo pills

Glucosamine
hydrochloride at a dose of 500 milligrams three times a day

Sodium
chondroitin at a dose of 400 milligrams three times a day

Combination
glucosamine and chondroitin

Celebrex
at a dose of 200 milligrams per day

It is common for a pain study to show that many patients report relief from
inactive placebo pills. And that happened here. Nearly 60% of patients given only placebo pills said they had less pain. So
did about 67% of patients treated with combination glucosamine and chondroitin. But that isn't what scientists call a significant
difference -- that is, there's more than a 7% chance the findings are just coincidence.{The point is that for one in 20 feeling a bit more relief from pain isn’t worth 6 pills a day and
a hundred dollars a month.If codiene worked in just 7% of the cases and only
somewhat, would it be taken for chronic pain?}

"I really feel the study is a negative study," Clegg says. "I would say to
patients that the safety data are really reassuring, the efficacy data are not."

When Clegg's team looked only at patients with moderate to severe pain. Only
54% of these patients got relief from placebo. But 79% reported relief from combination glucosamine and chondroitin. That
is a significant difference. But there's a problem, Clegg says. The study wasn't designed to look at just this group. The
effect here is based on only a small number of patients.

"About 20% of the study patients have moderate to severe pain," Clegg says.
"Interestingly, in that subgroup, the combination of glucosamine and chondroitin appeared to be effective in relieving pain.
I think this outcome is really interesting but just from a research standpoint. It is an exploratory, hypothesis-generating
finding -- not a finding on which to base treatment."

{While there is other studies supporting their effectiveness, none are that postive as to eliminate the placebo effect.When an innert placebo is given, the very taste of the pill is enough to inform its
taker which arm of the test they are in. A percentage of those tested will perform a
taste test to satisfy their curiosity. Thus every test when the control group receives an innert tasting placebo, it will demonstrate effectiveness, when the measure of effectiveness is self-reporting.}

SECOND
STUDY

What the pharmaceutical industry does for drug
research, those that promote alternative treatments do the same—and they have less scrutiny.Below is a meta-study done to evaluate glucosamine and chondrotin (very popular, alternative arthritis
treatment). Quantifiable results were not possible because of experimenter bias.

Study Selection Studies were included
if they were publishedor unpublished double-blind, randomized, placebo-controlledtrials of 4 or more
weeks' duration that tested glucosamineor chondroitin for knee or hip OA and reported extractable dataon
the effect of treatment on symptoms. Fifteen of 37 studieswere included in the analysis.

Data Extraction Reviewers performed
data extraction andscored each trial using a quality assessment instrument. Wecomputed an effect size
from the intergroup difference in meanoutcome values at trial end, divided by the SD of the outcomevalue
in the placebo group (0.2, small effect; 0.5, moderate;0.8, large), and applied a correction factor to reduce
bias.We tested for trial heterogeneity and publication bias and stratifiedfor trial quality and size.
We pooled effect sizes using a randomeffects model.

Data Synthesis Quality scores
ranged from 12.3% to 55.4%of the maximum, with a mean (SD) of 35.5% (12%).
Only 1 studydescribed adequate allocation concealment and 2 reported anintent-to-treat analysis. Most
were supported or performed bya manufacturer. Funnel plots showed significant asymmetry (P.01)compatible with publication bias. Tests for heterogeneity werenonsignificant after removing 1 outlier
trial. The aggregatedeffect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64)for glucosamine
and 0.78 (95% CI, 0.60-0.95) for chondroitin,but they were diminished when only high-quality or large trialswere considered. The effect sizes were relatively consistentfor pain and functional outcomes.

Conclusions Trials of glucosamine
and chondroitin preparationsfor OA symptoms demonstrate moderate to large effects, but qualityissues and likely publication bias suggest that these effectsare exaggerated. Nevertheless,
some degree of efficacy appearsprobable for these preparations.

Division of Rheumatology, Case Western Reserve University School of Medicine,
University Hospitals, Cleveland, Ohio, USA.

Division of Rheumatology, Case Western Reserve University School of Medicine, University Hospitals,
Cleveland, Ohio, USA.

There
are a sufficient number of short-term studies with these agents suggesting efficacy equal to that seen in the symptomatic
treatment of OA using NSAIDs. Two recent meta-analyses by McAlindon and colleagues and Towheed et al reviewed clinical trials
of glucosamine and chondroitin in the treatment of osteoarthritis. The study by McAlindon and co-workers included all double-blind
placebo-controlled trials of greater than 4 weeks' duration, testing oral or parenteral glucosamine or chondroitin for treatment
of hip or knee osteoarthritis. Thirteen trials (six with glucosamine, seven with chondroitin) met eligibility criteria. The
authors used global pain score or the Lequesne index in the index joint as the primary outcome measure and considered the
trial positive if improvement in the treatment group was equal to or greater than 25% compared with the placebo group, and
was significant (P < or = .05). All
13 studies reviewed were classified as positive, demonstrating large effects, compared with placebo (39.5% [S.D. 21.9] for
glucosamine, 40.2% [S.D. 6.4] for chondroitin). The authors concluded that clinical trials of these two
agents showed substantial benefit in the treatment of osteoarthritis but provided insufficient information about study design
and conduct to allow definitive evaluation. Towheed and colleagues reviewed nine randomized, controlled trials of glucosamine
sulfate in osteoarthritis. In seven of the randomized controlled trials, in which they compared glucosamine with placebo,
glucosamine was always superior. In two randomized controlled trials comparing glucosamine to ibuprofen, glucosamine was superior
in one and equivalent in one. Methodologic problems, including lack of standardized case definition of osteoarthritis and
lack of standardized outcome assessment led the authors to conclude that further studies are needed to determine if route
of administration is important and whether the therapeutic effect is site specific. A meta-analysis of chondroitin sulfate
trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or NSAID-controlled trials with
227 patients on chondroitin sulfate were entered into the analysis. All four studies showed chondroitin sulfate to be superior
to placebo, with respect to Lequesne index, visual analog scale for pain and medication consumption. Significant changes (P
< or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data demonstrated at
least 50% improvement in the study variables in the chondroitin treated group. Discrepancies in some of the study findings
reported in the literature may relate to the composition of the nutritional supplements used. Studies in the United States have revealed that a number of preparations claiming to contain certain doses of glucosamine or chondroitin sulfate
have significantly less (or none) of the dosages described. Accordingly, it is essential that studies performed with these
agents use preparations that are carefully defined in manufacture. The amounts generally administered are glucosamine, 1500
mg, and chondroitin sulfate, 1200 mg, daily. Although glucosamine has been described as effective when used alone, it is probably
reasonable to use the combination pending further studies. The average cost is approximately $30 to $45 per month. In the interim, what should physicians
tell their patients when they ask whether these agents are effective, or whether they should or should not take them? The
authors emphasize that these agents are not FDA-evaluated or recommended for the treatment of OA. They are available as health
food supplements, and the number of studies of toxicity, particularly with respect to long-term evaluations, is limited. The
pros and cons of these agents and the published data are described so that patients can make a reasonably informed decision
as to whether they wish to proceed with use of these agents in therapy. (ABSTRACT TRUNCATED)

Alternative medicine is like religion: faith, spurious claims, and damn the best reasoned
conclusion.